The present invention relates generally to the transport of hyperpolarized gases from one site to another, such as from a production site to a clinical use site. The hyperpolarized gases are particularly suitable for MR imaging and spectroscopy applications.
Inert gas imaging (xe2x80x9cIGIxe2x80x9d) using hyperpolarized noble gases is a promising recent advance in Magnetic Resonance Imaging (MRI) and MR spectroscopy technologies. Conventionally, MRI has been used to produce images by exciting the nuclei of hydrogen molecules (present in water protons) in the human body. However, it has recently been discovered that polarized noble gases can produce improved images of certain areas and regions of the body which have heretofore produced less than satisfactory images in this modality. Polarized Helium-3 (xe2x80x9c3Hexe2x80x9d) and Xenon-129 (xe2x80x9c129Xexe2x80x9d) have been found to be particularly suited for this purpose. Unfortunately, as will be discussed further below, the polarized state of the gases is sensitive to handling and environmental conditions and can, undesirably, decay from the polarized state relatively quickly.
Various methods may be used to artificially enhance the polarization of certain noble gas nuclei (such as 129Xe or 3He) over the natural or equilibrium levels, i.e., the Boltzmann polarization. Such an increase is desirable because it enhances and increases the MRI signal intensity, allowing physicians to obtain better images of the substances in the body. See U.S. Pat. No. 5,545,396 to Albert et al., the disclosure of which is hereby incorporated by reference as if recited in full herein.
A xe2x80x9cT1xe2x80x9d decay time constant associated with the hyperpolarized gas"" longitudinal relaxation is often used to characterize the length of time it takes a gas sample to depolarize in a given situation. The handling of the hyperpolarized gas is critical because of the sensitivity of the hyperpolarized state to environmental and handling factors and thus the potential for undesirable decay of the gas from its hyperpolarized state prior to the planned end use, e.g., delivery to a patient for imaging. Processing, transporting, and storing the hyperpolarized gasesxe2x80x94as well as delivering the gas to the patient or end userxe2x80x94can expose the hyperpolarized gases to various relaxation mechanisms such as magnetic field gradients, surface-induced relaxation, hyperpolarized gas atom interactions with other nuclei, paramagnetic impurities, and the like.
One way of reducing the surface-induced decay of the hyperpolarized state is presented in U.S. Pat. No. 5,612,103 to Driehuys et al. entitled xe2x80x9cCoatings for Production of Hyperpolarized Noble Gases.xe2x80x9d Generally stated, this patent describes the use of a modified polymer as a surface coating on physical systems (such as a Pyrex(trademark) container) which contact the hyperpolarized gas to inhibit the decaying effect of the surface of the collection chamber or storage unit. Other methods for reducing surface-induced decay are described in co-pending and co-assigned U.S. Patent application Ser. No. 09/163,721 to Zollinger et al., entitled xe2x80x9cHyperpolarized Noble Gas Extraction Methods, Masking Methods, and Associated Transport Containers.xe2x80x9d However, other relaxation mechanisms arise during production, handling, storage, and transport of the hyperpolarized gas. These problems can be particularly troublesome when storing the gases or transporting the hyperpolarized gas from a production site to a (remote) distribution and/or use site. In transit, the hyperpolarized gas can be exposed to many potentially depolarizing influences. There is, therefore, a need to provide improved ways to transport hyperpolarized gases so that the hyperpolarized gas is not unduly exposed to depolarizing effects during transport. Improved storage and transport methods and systems are desired so that the hyperpolarized product can retain sufficient polarization to allow effective imaging at delivery when stored or transported over longer transport distances in various (potentially depolarizing) environmental conditions, and for longer time periods from the initial point of polarization than has been viable previously.
One design used to provide a homogeneous field in a unit for transporting and storing hyperpolarized gas products is proposed by Hasson et al. in U.S. patent application Ser. No. 09/333,571 entitled xe2x80x9cHyperpolarized Gas Containers, Solenoids, Transport and Storage Devices and Associated Transport and Storage Methods.xe2x80x9d This technique comprises a durable, safe, and convenient transport unit. However, a magnetic field generator within the transport unit used for generating the hyperpolarized gas magnetic holding field requires power to operate it. During transport or in storage, a convenient source of power may be difficult to find. Additionally, batteries with lengthy lifetimes suitable for hyperpolarized gas transport and storage can be heavy and are often large.
Another alternative is proposed by Aidam et al. in WO 99/17304. This reference proposes configuring a magnetically shielded container using opposing pole shoes to provide a unit for holding and transporting a chamber of polarized gas. Unfortunately, the shielded container is designed so as to require removal of one of the pole shoes to remove the gas chamber, thereby potentially sacrificing the homogeneity of the field. Additionally, the pole shoes can be dented or permanently magnetized during transport and storage. Physical deformation of the pole shoes which occurs during transport or normal use can unfortunately permanently destroy the homogeneity of the magnetic field. Furthermore, the pole shoes (which as described by Aidam et al. comprise mu metal or soft iron) can display hysteresis characteristics. This hysteresis can cause the pole shoes to be permanently magnetized if placed next to a magnetic field source, thereby acting as its own magnet and potentially deleteriously affecting the homogeneity of the resulting permanent magnet field.
A third alternative is proposed in U.S. patent application Ser. Nos. 08/989,604 and 09/210,020 to Driehuys et al. In these two patent applications, a magnetic field generator is described for the transport of hyperpolarized frozen xenon. The embodiment proposed by Driehuys et al. comprises a relatively small magnet yoke and two permanent magnets mounted opposite one another on the magnet yoke. This configuration produces a magnetic field with high field strength but relatively low homogeneity. While high magnetic field strength alone can generally maintain a highly hyperpolarized state in a solid hyperpolarized gas product, thawing prior to use produces a gaseous xenon product, which then typically requires that the field be homogeneous to reduce the likelihood of rapid depolarization due to gradient-induced relaxation.
It is therefore an object of the present invention to provide a transport unit which can hold quantities of hyperpolarized gas for extended periods of time, such that the hyperpolarized gas is sufficiently viable to produce clinically useful images at a spatially and/or temporally separated point in time from the point of polarization.
It is also an object of the present invention to configure a transport unit such that it can be used to transport gas in a commercial shipping vehicle and/or store gas over relatively long periods of time (the latter particularly for when the polarized gas is not intended to be remotely shipped).
Another object of the present invention is to shield a quantity of hyperpolarized gas from deleterious environmentally-induced depolarizing events during transport and/or storage.
An additional object of the present invention is to configure a transport unit with permanent magnets which does not require disassembly to dispense the hyperpolarized gas therefrom or to insert hyperpolarized gas in containers therein.
It is also an object of the present invention to create a transport unit which is lightweight, compact, and easily transportable to facilitate ease of transport and storage.
An additional object of the present invention is to provide a magnetic field generator or source which does not require external power.
It is another object of the present invention to configure a transport unit to reduce the external force associated with shock, vibration, and/or other mechanical collisions that are input into or transmitted to containers of hyperpolarized gas held within the transport unit.
It is also an object of the present invention to provide a portable unit for storing or transporting hyperpolarized gas held in a plurality of separate containers therein.
It is another object of the present invention to size and configure a transport unit to provide a suitable environment for storing and transporting large pressurized multi-bolus containers of hyperpolarized gas.
An additional object of the present invention is to configure a transport unit with an easily accessible means for interrogating the polarized state of the polarized gas held therein using nuclear magnetic resonance (NMR), in order to measure the polarization of the gas, or to measure the decay rate of the polarization.
An additional object of the present invention is to reduce hyperpolarization relaxation due to gas-gas relaxation and/or gradient relaxation by diluting the hyperpolarized gas with a buffer gas.
These and other objects are satisfied by the present invention by configuring a transport unit with a series of relatively lightweight permanent magnets arranged to provide a region of homogeneity for a quantity of hyperpolarized gas held therein. In particular, a first aspect of the present invention is directed to a transport unit which includes a housing and at least four discrete spaced-apart permanent magnets which are configured such that they are arranged in spaced-apart relationship about a longitudinally extending axis defining a center therebetween. The permanent magnets provide a magnetic field with a region of homogeneity substantially centered with respect to the longitudinal axis and the magnets are oriented such that the field direction they produce are substantially perpendicular to the longitudinal axis. Additionally, the transport unit includes at least one container, sized and configured to hold a quantity of hyperpolarized gas, positioned proximate to the region of homogeneity.
In one preferred embodiment, the spaced-apart permanent magnets are elongated and positioned in spaced-apart circumferential relationship to longitudinally extend a distance sufficient to define a substantially cylindrical volume projected in space. In another preferred embodiment, the spaced-apart permanent magnets are positioned in spaced-apart circumferential relationships to define a spherical volume projected in space.
Another aspect of the present invention is directed toward a transport unit for transporting containers of hyperpolarized gas products. This transport unit includes first and second spaced-apart opposing end plates and a plurality of spaced-apart elongated permanent magnets having opposing first and second ends. Each of the permanent magnets are positioned to extend substantially linearly between the first and second opposing end plates to provide a magnetic field with a region of homogeneity therebetween. Additionally, a chamber (configured to hold a quantity of hyperpolarized gas) is preferably positioned between the first and second end plates within the region of homogeneity.
Preferably, the spaced-apart elongated permanent magnets are positioned in a spaced-apart circumferential relationship to define a cylinder projected in space. In one preferred embodiment, the plurality of permanent magnets are rubber strip magnets and each magnet is structurally secured to a longitudinally extending support member which is attached to each of the opposing end plates. Preferably, the magnets are configured to remain fixedly attached to the end plates via the support members during installation and removal of the gas container(s) into and out of the transport unit. It is also preferred that the permanent magnets be substantially circumferentially spaced apart about a circle with a center coincident with a longitudinal center axis extending therethrough. The center of the longitudinal center axis defines the center of a holding volume in the transport unit, and a vertical diametrical line drawn through the center of the circle between the upper and lower parts thereof defines a first vertical axis. In this preferred embodiment, the elongated magnets are oriented such that the magnetic north pole surface is in a fixed angular relationship with the first vertical axis. Additionally, a plurality of supplementary magnets can be positioned on end portions of selected elongated magnets enlarge the region of homogeneity therein.
Another aspect of the present invention is directed toward a transport unit for transporting hyperpolarized gas using discrete magnets. The unit includes at least one gas chamber configured to hold a quantity of hyperpolarized gas therein, a first upstanding end wall comprising a first set of spaced-apart discrete permanent magnets positioned thereon, and a second upstanding end wall positioned in the transport unit spaced apart from and opposing the first wall to define a gas enclosure volume for holding the gas chamber therebetween. The second upstanding wall comprises a second set of spaced-apart discrete permanent magnets positioned thereon. Additionally, the first and second magnet sets are circumferentially arranged about two corresponding circles with corresponding first diameters and aligned centers on the first and second walls, respectively, and each of the discrete permanent magnets has a magnetic north and south pole associated therewith. Furthermore, the first magnet set is arranged on the first wall such that the magnetic north pole of each magnet in the first magnet set is directed toward the center of the circle that the first magnet set is arrange thereabout, and the magnetic south pole of each magnet in the second magnet set is directed toward the center of the circle around which the second magnet set is arranged. Each of the permanent magnets in each of the first and second magnet sets are arranged to laterally extend toward the other a minor distance to define a central free space with a magnetic holding field having a region of homogeneity therebetween.
Preferably, the transport unit also includes a housing, where the housing is spaced apart a predetermined separation distance (preferably at least about 2 inches) from the perimeter of the gas chamber holding a major volume of the hyperpolarized gas therein. The transport unit also preferably includes a third supplementary set of magnets arranged to be circumferentially spaced apart about a third circle having a second diameter, wherein the set of supplementary magnets is positioned intermediate the first and second magnet sets. Preferably, the second diameter is larger than the first diameter. The magnets in the supplementary set of magnets have a north pole and a south pole, and the north pole of the supplementary magnets are oriented to point normal to the plane defined by the third circle and in the direction of a plane defined by the first circle.
Another aspect of the present invention is directed toward a method of fabricating a cylindrically shaped magnetic field volume. This method involves rolling a flexible magnetic sheet into a first hollow cylinder such that the ends abut. Then, a magnetic field is applied to the cylindrically configured flexible magnetic sheet which is then unrolled. Finally, the flexible magnetic sheet is rerolled into a second hollow cylinder such that the ends abut, and such that the sides are reversed, i.e., the side that was inside the first hollow cylinder is positioned to define the outer side of the second hollow cylinder.
An additional aspect of the present invention is directed toward a transport unit for transporting a quantity of hyperpolarized gas using a magnetic hollow cylinder to generate a holding field for a chamber of hyperpolarized gas. The transport unit includes at least one container for holding hyperpolarized gas, a flexible material layer having an applied magnetization, wherein the flexible layer is configured as a cylinder having magnetic north and south poles and a magnetic field strength. The flexible material layer defines a homogenous magnetic holding field for the container and fits inside a housing.
Preferably, the housing is configured and sized to be at least 2 inches away from the walls of the gas container. Furthermore, the flexible material is magnetized such that the direction of the magnetic north varies about the circumference of the cylinder. The cylinder also includes a continuous surface represented by a plurality of adjacent points drawn in space. At each point on the flexible cylinder, there is a direction of magnetic north and a first vertical axis which intersects the point. Additionally, each point has a second vertical axis associated with it which diametrically extends to bisect opposing top and bottom surfaces of the cylinder. The flexible cylinder is preferably configured such that at any point, a first angle between the magnetic north direction and the first vertical axis is twice the magnitude of a second angle between the second vertical axis and a line to the point from the center of the second diametrical axis.
The present invention is advantageous because it enables hyperpolarized gas to withstand travel from a production site to a remote use site in a hyperpolarized state which is still capable of producing clinically useful images at the remote site. To do this, the present invention shields the gas from deleterious ambient external magnetic fields while creating its own internal holding field for the hyperpolarized gas without requiring an external or internal power source. Advantageously, this holding field comprises permanent magnets, which are lightweight and easy to manufacture. Additionally, the magnetic holding field does not need to be disturbed to insert or remove a gas chamber, which advantageously allows the magnetic holding field to carry several gas chambers at one time without deleterious affects on the remaining chambers in the holding field when one is removed therefrom.